Iron Complexes with Chiral N/P Macrocycles as Catalysts for Asymmetric Transfer Hydrogenation

Abstract

The present account describes the development of chiral, C 2 -symmetric N/P macrocyclic ligands that attune to the size and electronic properties of the iron(II) ion to give robust complexes under catalysis conditions. This is not trivial, as the complexes of base metals are substantially less stable than those of precious metals. Also, as these N 2 P 2 macrocycles feature stereogenic P atoms, the control of the stereochemistry at phosphorus is a key synthetic issue. Still, as the macrocyclic effect was insufficient to give robust catalysts under hydrogen transfer conditions, we had to dig deeper into the toolbox of coordination chemistry and use strong-field ancillary ligands other than CO, specifically isonitriles, which additionally offer a further handle to tune the catalyst. The reward was the discovery of the first iron(II) catalyst for the asymmetric transfer hydrogenation of polar double bonds that is highly enantioselective for a broad scope of substrates.

Chiral Benzoins via Asymmetric Transfer Hemihydrogenation of Benzils: The Detail that Matters

“…Overall, hydride [FeH­(CNCEt 3 )­( 1 )]­BF 4 ( 3 ) catalyzes the (hemi)­hydrogenation (ATH) of benzils ( 4 ) with enantioselectivity comparable to that of enzymatic methods, but with the advantage that both benzoin enantiomers are accessible. Concerning the limitations of the method, we have prepared an N 2 P 2 macrocycle bearing mesityl substituents instead of phenyl on the P atoms to optimize the stereoselection with unsymmetrically substituted benzils. However, preliminary tests with 1-(4-fluorophenyl)-2-(2-methoxyphenyl)­ethane-1,2-dione as a substrate have shown low regioselectivity (1:1.5 ratio) .…”

Chiral Iron Complexes in Asymmetric Organic Transformations

“…The addition of one more carbon atom to the bridge between the two phosphines (ligand L5 ), leading to a six‐membered‐chelate P−Fe−P ring in a more rigid chair conformation, resulted in higher selectivities of the resulting iron complexes: [Fe(CNCEt 3 ) 2 ( L5 )] and [Fe(CNN i Pr 2 ) 2 ( L5 )] ( 16 a and 16 b , Scheme 7A) converted acetophenone to ( R )‐1‐phenylethanol in high yield with 98% ee and 99% ee , respectively [32] . Different aryl ketones were reduced with excellent selectivity (>90% ee, Scheme 7B) [33] …”

“…[32] Different aryl ketones were reduced with excellent selectivity (> 90% ee, Scheme 7B). [33] In order to expand the scope of the catalysis to base-sensitive substrates, hydride complex [FeH (CNCEt 3 )(L5)] (17, Figure 8) was also prepared and tested in the ATH of ketones, as well as in the reduction of 1,2-diketones to α-hydroxyketones, which undergo racemization in basic media. [34] The enantiomeric excesses obtained in the reduction of simple ketones were similar to those achieved with catalysts 16 a and 16 b, with slightly lower conversions.…”

Configurational landscape of chiral iron(ii) bis(phosphane) complexes

“…[11][12][13] Among them, the design and preparation of welldefined chiral hydrido or dihydrogen iron complexes directed to catalytic asymmetric hydrogenation of ketones have attracted much attention. [13][14][15][16][17][18][19][20][21][22][23][24][25] Alternatively, the active species can be in situ generated in the catalytic process by combining a chiral ligand with cheap, stable and readily available iron compounds. 9 As a paradigmatic example, Beller and coworkers reported one of the firsts examples of iron (II)-catalyzed asymmetric hydrosilylation of ketones, with excellent enantioselectivities obtained from highly hindered aromatic ketones by using a combination of Fe(OAc)2, two equivalents of (S,S)-Me-DuPhos, and a reducing agent ((EtO)2MeSiH or PMHS (PMHS = polymethylhydrosiloxane)) in THF.…”